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6  structures 107  species 0  interactions 147  sequences 6  architectures

Family: Siah-Interact_N (PF09032)

Summary: Siah interacting protein, N terminal

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This is the Wikipedia entry entitled "Siah interacting protein N-terminal domain". More...

Siah interacting protein N-terminal domain Edit Wikipedia article

Siah-Interacting Protein, N terminal domain
PDB 1ysm EBI.jpg
NMR structure of N-terminal domain (residues 1-77) of Siah-interacting protein.
Identifiers
Symbol Siah-Interact_N
Pfam PF09032
InterPro IPR015120

In molecular biology the protein domain, Siah interacting protein N-terminal domain is found at the N-terminal of the protein, Siah interacting protein (SIP). It has a helical hairpin structure with a hydrophobic core which is further stabilised by an arrangement of side chains contributed by the two amphipathic helices. The function of this domain remains to be fully elucidated, but it is known to be vital for interactions with Siah. It has also been hypothesised that SIP can dimerise through this N-terminal domain.[1]

Function[edit]

SIP protein[edit]

The SIP protein has a role as an adaptor protein, it links the E3 ubiquitin ligase activity of Siah-1 with Skp1 and Ebi F-Box protein in the degradation of beta-catenin, a transcriptional activator of TCF/LEF genes. This is important for signalling that the protein needs to undergo proteolysis at the 26s proteosome.[2]

N-terminal domain of SIP protein[edit]

More specifically, the N-terminal domain of the SIP protein is a dimerisation domain.[2] Its precise function is yet to be elucidated. More recent studies have shown that when the N-terminal domain is shortened, or in other words truncated by a nonsense mutation, it results in an increase in the import of SIP into the nucleus and enhances its proapoptotic effect (programmed cell death).[3] These findings indicate that the SIP protein and in particular the N-terminal domain may provide important information about drug resistance.

Structure[edit]

The N terminal domain is a dimer. Each monomer has an alpha helical hairpin in which the two alpha helices are connected by a tight 3-residue turn. Hairpins from two monomers associate as a four-helix bundle.[2]

References[edit]

  1. ^ Bhattacharya S, Lee YT, Michowski W, Jastrzebska B, Filipek A, Kuznicki J, Chazin WJ (July 2005). "The modular structure of SIP facilitates its role in stabilizing multiprotein assemblies". Biochemistry 44 (27): 9462–71. doi:10.1021/bi0502689. PMID 15996101. 
  2. ^ a b c Santelli E, Leone M, Li C, Fukushima T, Preece NE, Olson AJ et al. (2005). "Structural analysis of Siah1-Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex.". J Biol Chem 280 (40): 34278–87. doi:10.1074/jbc.M506707200. PMID 16085652. 
  3. ^ Luo J, Yang J, Yu BY, Liu W, Li M, Zhuang SM (2010). "Identification of Siah-interacting protein as a potential regulator of apoptosis and curcumin resistance.". Oncogene 29 (48): 6357–66. doi:10.1038/onc.2010.358. PMID 20729913. 

This article incorporates text from the public domain Pfam and InterPro IPR015120

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Siah interacting protein, N terminal Provide feedback

The N terminal domain of Siah interacting protein (SIP) adopts a helical hairpin structure with a hydrophobic core stabilised by a classic knobs-and-holes arrangement of side chains contributed by the two amphipathic helices. Little is known about this domain's function, except that it is crucial for interactions with Siah. It has also been hypothesised that SIP can dimerise through this N terminal domain [1].

Literature references

  1. Bhattacharya S, Lee YT, Michowski W, Jastrzebska B, Filipek A, Kuznicki J, Chazin WJ; , Biochemistry. 2005;44:9462-9471.: The modular structure of SIP facilitates its role in stabilizing multiprotein assemblies. PUBMED:15996101 EPMC:15996101


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR015120

The N-terminal domain of Siah interacting protein (SIP) adopts a helical hairpin structure with a hydrophobic core stabilised by a classic knobs-and-holes arrangement of side chains contributed by the two amphipathic helices. Little is known about this domain's function, except that it is crucial for interactions with Siah. It has also been hypothesised that SIP can dimerise through this N-terminal domain [PUBMED:15996101].

Domain organisation

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Alignments

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  Seed
(10)
Full
(147)
Representative proteomes NCBI
(136)
Meta
(0)
RP15
(23)
RP35
(36)
RP55
(61)
RP75
(89)
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  Seed
(10)
Full
(147)
Representative proteomes NCBI
(136)
Meta
(0)
RP15
(23)
RP35
(36)
RP55
(61)
RP75
(89)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Curation and family details

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Seed source: pdb_1ysm
Previous IDs: none
Type: Domain
Author: Mistry J, Sammut SJ
Number in seed: 10
Number in full: 147
Average length of the domain: 69.90 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 31.30 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.3 21.3
Trusted cut-off 21.3 21.4
Noise cut-off 20.8 21.0
Model length: 79
Family (HMM) version: 6
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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Siah-Interact_N domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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